Bowley, K.A., Morton, M.J., Hunter, M. and Sandle, G.I. (2003) Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells. Gut, 52 (6). pp. 854-860. ISSN 0017-5749
Available under licence : See the attached licence file.
BACKGROUND: Aldosterone has a rapid, non-genomic, inhibitory effect on macroscopic basolateral K+ conductance in the human colon, reducing its capacity for Cl− secretion. The molecular identity of the K+ channels constituting this aldosterone inhibitable K+ conductance is unclear.
AIM: To characterise the K+ channel inhibited by aldosterone present in the basolateral membrane of human colonic crypt cells.
METHODS: Crypts were isolated from biopsies of healthy sigmoid colon obtained during colonoscopy. The effect of aldosterone on basolateral K+ channels, and the possible involvement of Na+:H+ exchange, were studied by patch clamp techniques. Total RNA from isolated crypts was subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific to intermediate conductance K+ channels (KCNN4) previously identified in other human tissues.
RESULTS: In cell attached patches, 1 nmol/l aldosterone significantly decreased the activity of intermediate conductance (27 pS) K+ channels by 31%, 53%, and 54% after 1, 5 and 10, minutes, respectively. Increasing aldosterone concentration to 10 nmol/l produced a further 56% decrease in channel activity after five minutes. Aldosterone 1–10 nmol/l had no effect on channel activity in the presence of 20 µmol/l ethylisopropylamiloride, an inhibitor of Na+:H+ exchange. RT-PCR identified KCNN4 mRNA, which is likely to encode the 27 pS K+ channel inhibited by aldosterone.
CONCLUSION: Intermediate conductance K+ channels (KCNN4) present in the basolateral membranes of human colonic crypt cells are a target for the non-genomic inhibitory effect of aldosterone, which involves stimulation of Na+:H+ exchange, thereby reducing the capacity of the colon for Cl− secretion.
|Copyright, Publisher and Additional Information:||Copyright © 2003 BMJ Publishing Group Ltd & British Society of Gastroenterology|
|Institution:||The University of Leeds|
|Academic Units:||The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)|
|Depositing User:||Milburn Gemma|
|Date Deposited:||13 Mar 2006|
|Last Modified:||21 Jun 2014 18:49|